丙酮酸乙酯对宫内感染致脑损伤新生仔鼠12-脂氧合酶表达和细胞凋亡的影响

目的研究丙酮酸乙酯(ethyl pyruvate,EP)对宫内感染致新生仔鼠脑损伤12-脂氧合酶表达和细胞凋亡的影响。方法 36只孕鼠随机分为LPS组、EP组、NS组,每组各12只。LPS组:于孕17天、18天孕鼠连续两天腹腔注射脂多糖380μg/kg;EP组:相同的方法制备孕鼠宫内感染模型,并于孕鼠腹腔注射LPS后立即给予腹腔注射EP 40mg/kg;NS组:给予等量生理盐水腹腔注射。孕鼠分娩后,取胎盘进行HE染色,以观察宫内感染情况。剔除早产鼠,随机选取各组仔鼠36只,分别于出生后1d、3d、7d进行检测,观察脑组织12-脂氧合酶(12-lipoxygenase,12-LOX)的表达和神经细胞凋亡情况。结果与NS组比较,LPS组孕鼠胎盘组织可见明显的炎性细胞浸润,血管充血等病理改变;与LPS组相比较,EP组仔鼠出生后1、3、7d脑组织12-LOX的表达量均低于LPS组(P0.05)、神经细胞凋亡指数均也均低于LPS组(P0.05)。结论 EP对宫内感染致脑损伤新生仔鼠的脑组织具有保护作用,可能与12-LOX表达水平和细胞凋亡降低相关。

Protective effects of ethyl pyruvate on expressions of 12-lipaxygenase and apoptosis on rat's offspring's damaged brain caused by intrauterine infection.

Objective To study the effect of ethyl pyruvate(EP) in the expression of 12-lipoxygenase(12-LOX) and apoptosis changes on rat's offspring's damaged brain caused by intrauterine infection. Methods Pregnant wistar rats of lipopolysaccharide(LPS) group were consecutively injected with lipopolysaccharide 380 μg/(kg·day)] intraperitoneally.Pregnant Wistar rats of EP group were consecutively injected with LPS intraperitoneally,and EP was administrated intraperitoneally at a dose of 40 mg/kg immediately.12 pregnant rats were injected with normal saline intraperitoneally as control group.After the delivery of pups,thirty-six pups were selected in every group randomly.placenta from rats of LPS group was taken for hematoxylline-eosin (HE) staining to confirm its intrauterine infection.12-LOX expression in brain tissue was studied through immunohistochemical and western-blot analysis.TUNEL was used to observe the pathological changes of the brain tissue. Results Obvious pathological changes were observed in the placenta in the infection groups.The expression of apoptosis was lower in EP group and NS group than in the LPS group (P<0.05),and lower in NS group than that in the EP group (P<0.05).The expression of 12-lipoxygenase was lower in EP group and NS group than that in the LPS group (P<0.05),and lower in NS group than that in the EP group (P<0.05). Conclusion EP confers potent protection against LPS-induced brain injury via significantly reduced the expression of 12-LOX and anti-apoptotic properties.